Unmet Gout Tx Targets: Stay or Switch?

Study's chief message is that gout management in U.S. is suboptimal

Patients with gout who switched to febuxostat (Uloric) after an inadequate response to allopurinol were more successful at achieving the target serum urate level than those who continued on allopurinol, a retrospective study found.

In a multivariable analysis, patients who switched had a 40% greater likelihood of lowering their serum urate level to under 6 mg/dL (OR 1.403, 95% CI 1.166-1.687, P<0.001) compared with those who remained on allopurinol, according to Jasvinder A. Singh, MD, of the University of Alabama at Birmingham, and colleagues.

They also had an 82% greater chance of lowering the level further, to under 5 mg/dL (OR 1.825, 95% CI 1.510-2.205, P<0.001), the researchers reported in the December Journal of Clinical Rheumatology.

"Reaching a goal of less than 6 mg/dL is widely accepted as critical in gout management and leads to generally excellent outcomes with continued patient medication adherence," said Ted Fields, MD, of the Hospital for Special Surgery in New York City, who was not involved in the study.

Despite the finding that uric acid goals were more often met by patients who switched to febuxostat, the study authors pointed out that dosage titration occurred in a minority of patients in the two groups -- in only 15% of the allopurinol continuers and in 21% of the febuxostat switchers.

"Prior studies have shown that only about 40% of patients reach a uric acid goal of less than 6 mg/dL on 300 mg allopurinol," Fields pointed out. The drug is FDA approved for use in dosages up to 800 mg/day.

Various guidelines recommend xanthine oxidase inhibitors, a class of drugs that includes both allopurinol and febuxostat, as first-line therapy for gout.

"In practice, allopurinol has been the first-line treatment, and when it fails or is associated with adverse effects, febuxostat is the second urate lowering therapy option considered by most providers. To our knowledge, studies comparing the effectiveness ... of continuing allopurinol versus switching therapy to febuxostat in the real-world setting have not been done," Singh and colleagues wrote.

Therefore, the researchers analyzed claims data from commercial and Medicare Advantage health plans in the Optum Research Database, which includes more than 50 million enrollees.

They identified 5,543 who had at least one laboratory test for serum uric acid and at least one pharmacy claim for either allopurinol or febuxostat during the years 2009 to 2012.

A total of 748 had switched from allopurinol to febuxostat because of a lack of efficacy or intolerance, and 4,795 continued on allopurinol. The index date was the date when the first prescription was filled during the study period.

For both switchers and continuers, the majority of patients were male and had commercial insurance. Mean age was higher for switchers (57 versus 55, P=0.003).

Among the allopurinol continuers, the most common dose was 300 mg/day, in 64%. Doses below that were used by 31%, and in only 5% was the dose higher than 300 mg/day. Among the switchers, the allopurinol dose had been 300 mg or less in 93%.

The most common dose of febuxostat among switchers was 40 mg/day (77%), while in 23% it was 80 mg/day (23%).

Patients who switched from allopurinol to febuxostat had significantly higher serum uric acid levels before the index date (8 mg/dL vs 6.6 mg/dL, P<0.001), and had a greater decline in urate levels after switching (1.8 mg/dL) than did those who continued on allopurinol (0.4 mg/dL, P<0.001).

The target goal of a serum uric acid level below 6 mg/dL was achieved by 62.2% of switchers and 58.7% of continuers, which was not a significant difference, while levels below 5 mg/dL were seen in 38.9% versus 29.6% (P<0.001).

The authors noted that a limitation of the study was its reliance on claims data, which meant that medication adherence and dosing were not measured.

"However, these comparative effectiveness results from this 'real world' [study] are still valid, because we are comparing effectiveness, which incorporates factors such as adherence, dose titration, and so on. However, the reader must interpret these findings being from an effectiveness study, not an efficacy study," the authors cautioned.

"Considering all these factors, we are left to speculate on the reasons for their findings and the implications for management," Fields told MedPage Today.

"No doubt one conclusion is that greater efforts at allopurinol dose titration will benefit patients," he said.

"The chief message of this study is that gout management in the U.S. is quite suboptimal, and that an individualized approach to patients that gets them to uric acid goal, whether by titrating allopurinol or switching to febuxostat, should lead to better gout outcomes," Fields stated.

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